Divergent Synthesis of Alcohols and Ketones via Cross‐Coupling of Secondary Alcohols under Manganese Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(26)

Published: April 21, 2023

A homogeneous manganese-catalyzed cross-coupling of two secondary alcohols for the divergent synthesis γ-disubstituted and β-disubstituted ketones is reported. Employing well-defined Mn-MACHOPh as catalyst, this novel protocol has a broad substrate scope with good functional group tolerance affords diverse library valuable disubstituted in moderate to yields. The strong influence reaction temperature on selective formation alcohol products was theorized preliminary DFT studies. Studies have shown that Gibbs free energy thermodynamically more favourable than corresponding at lower temperature.

Language: Английский

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Iridium-Catalyzed Enantioselective Transfer Hydrogenation of 1,1-Dialkylethenes with Ethanol: Scope and Mechanism

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 3427 - 3437

Published: Jan. 20, 2024

Despite half a century's advance in the field of transition-metal-catalyzed asymmetric alkene hydrogenation, enantioselective hydrogenation purely alkyl-substituted 1,1-dialkylethenes has remained an unmet challenge. Herein, we describe chiral PCNOx-pincer iridium complex for transfer this class with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels enantioselectivity can be achieved reactions substrates secondary/primary and primary/primary alkyl combinations. The catalyst is further applied to redox isomerization disubstituted alkenols, producing stereocenter remote resulting carbonyl group. Mechanistic studies reveal dihydride species, (PCNOx)Ir(H)2, as catalytically active intermediate, which decay dimeric species (κ3-PCNOx)IrH(μ-H)2IrH(κ2-PCNOx) via ligand-remetalation pathway. deactivation under conditions H2 much faster than that EtOH, explains why (PCNOx)Ir effective but ineffective hydrogenation. suppression di-to-trisubstituted by regioselective 1,2-insertion partly responsible success system, underscoring critical role played pincer ligand 1,1-dialkylethenes. Moreover, computational elucidate significant influence London dispersion interaction between substrate on control, illustrated complete reversal stereochemistry through cyclohexyl-to-cyclopropyl group substitution substrates.

Language: Английский

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Challenging Task of Ni-Catalyzed Highly Regio-/Enantioselective Semihydrogenation of Racemic Tetrasubstituted Allenes via a Kinetic Resolution Process

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(11), P. 7419 - 7430

Published: March 6, 2024

The first earth-abundant transition metal Ni-catalyzed highly regio- and enantioselective semihydrogenation of racemic tetrasubstituted allenes via a kinetic resolution process as challenging task was well established. This protocol furnishes expedient access to diversity structurally important enantioenriched chiral allylic molecules with high regio-, enantio-, Z/E-selectivity. Remarkably, this proceeded one carbon–carbon double bond allenes, which regioselective complementary the Rh-catalyzed asymmetric version. Deuterium labeling experiments density functional theory (DFT) calculations were carried out reveal reasonable reaction mechanism explain regio-/stereoselectivity.

Language: Английский

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Organometallic Mn(I) Complexes in Asymmetric Catalytic (Transfer) Hydrogenation and Related Transformations

ChemCatChem, Journal Year: 2024, Volume and Issue: 16(14)

Published: March 7, 2024

Abstract Direct asymmetric hydrogenation (AH) and transfer (ATH) are among the most efficient approaches to produce chiral building blocks. Recently, these types of transformations have witnessed a shift towards use molecular catalysts based on earth‐abundant transition metals due their ready availability, economic advantage, novel properties. With particular regard manganese, catalyst development has seen both efficiency substrate scope in AH ATH greatly improved, with emergence large number well‐defined Mn‐complexes employed this field. The reaction includes C=O bonds, reduction C=N bonds reductive C=C bonds. Herein, our survey area focuses catalytic activity such complexes, versatility routes convert substrates target molecules. We consider collected findings article will be helpful reader by providing an insight into ligand design, thereby aiding future development. Moreover, review is aimed at highlighting remarkable progress made last seven years manganese complexes for enantioselective reduction.

Language: Английский

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X-type silyl ligands for transition-metal catalysis

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(9), P. 4648 - 4673

Published: Jan. 1, 2024

This review summarizes the developments of X-type silyl ligands for transition-metal catalysis, elucidating unique features σ-donating ability and trans -influence silyl–metal catalysts.

Language: Английский

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Bimetallic Ru/Ru‐Catalyzed Asymmetric One‐Pot Sequential Hydrogenations for the Stereodivergent Synthesis of Chiral Lactones

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: March 21, 2024

Abstract Asymmetric sequential hydrogenations of α ‐methylene γ ‐ or δ ‐keto carboxylic acids are established in one‐pot using a bimetallic Ru/Ru catalyst system, achieving the stereodivergent synthesis all four stereoisomers both chiral and ‐lactones with two non‐vicinal carbon stereocenters high yields (up to 99%) excellent stereoselectivities >99% ee >20:1 dr). The compatibility Ru systems is investigated detail, it found that basicity reaction system plays key role hydrogenation processes. protocol can be performed on gram‐scale low loading 11000 S/C) resulting products allow for many transformations, particularly several intermediates useful preparation drugs natural products.

Language: Английский

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Fe/Thiol Cooperative Hydrogen Atom Transfer Olefin Hydrogenation: Mechanistic Insights That Inform Enantioselective Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(25), P. 17296 - 17310

Published: June 14, 2024

Asymmetric hydrogenation of activated olefins using transition metal catalysis is a powerful tool for the synthesis complex molecules, but traditional catalysts have difficulty with enantioselective reduction electron-neutral, electron-rich, and minimally functionalized olefins. Hydrogenation based on radical, metal-catalyzed hydrogen atom transfer (mHAT) mechanisms offers an outstanding opportunity to overcome these difficulties, enabling mild challenging selectivity that complementary hydrogenations H2. Further, mHAT presents asymmetric induction through cooperative (cHAT) chiral thiols. Here, we report insights from mechanistic study iron-catalyzed achiral cHAT reaction leverage deliver stereocontrol Kinetic analysis variation silane structure point hydride iron as likely rate-limiting step. The data indicate selectivity-determining step quenching alkyl radical by thiol, which becomes more potent H donor when coordinated iron(II). resulting iron(III)–thiolate in equilibrium other species, including FeII(acac)2, shown be predominant off-cycle species. enantiodetermining nature thiol trapping enables net commercially available glucose-derived catalyst up 80:20 enantiomeric ratio. To best our knowledge, this first demonstration via mHAT. These findings advance understanding act proof principle development reactions.

Language: Английский

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NiH-Catalyzed Reductive Hydrocarbonation of Enol Esters and Ethers

CCS Chemistry, Journal Year: 2021, Volume and Issue: 4(2), P. 605 - 615

Published: March 2, 2021

Open AccessCCS ChemistryRESEARCH ARTICLE1 Feb 2022NiH-Catalyzed Reductive Hydrocarbonation of Enol Esters and Ethers Xiao-Xu Wang†, Lu Yu†, Xi Lu, Zhi-Lin Zhang, De-Guang Liu, Changlin Tian Yao Fu Wang† Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Urban Pollutant Conversion, Anhui Province Biomass Clean Energy, Center Excellence in Molecular Synthesis CAS, University Science Technology China, 230026 Institute Comprehensive Center, 230031 , Yu† High Magnetic Field Laboratory, Chinese Academy Sciences, *Corresponding authors: E-mail Address: [email protected] Zhang Liu School Life 230027 https://doi.org/10.31635/ccschem.021.202000760 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Chiral dialkyl carbinols their derivatives are significant synthetic building blocks organic chemistry related fields. The development convenient efficient methods access these compounds has long been an important endeavor. Herein, we report a NiH-catalyzed reductive hydroalkylation hydroarylation enol esters ethers. α-Oxoalkyl organonickel species were generated situ catalytic mode then participated cross-coupling with alkyl or aryl halides. This approach enabled C(sp3)–C(sp3) C(sp3)–C(sp2) bond formation under mild conditions simple operations, thereby boosting broad substrate scope good functional compatibility. enantioenriched accessed asymmetric version. Mechanistic studies demonstrated that this reaction proceeded through syn-addition Ni–H intermediate ester high regio- enantioselectivity. Download figure PowerPoint Introduction Enantiomerically pure alcohols common They also frequent substructures natural products drug molecules (Scheme 1a). For time, considerable efforts have devoted synthesis modes 1b).1–6 However, some restrictions remain: reported suitable kinetic resolution racemic was limiting. instance, hydrogenation ketones widely used industrial production. Nonetheless, process barely yielded satisfactory performance ketones, especially when encountered generation bear two aliphatic substituents minimally differentiated steric electronic properties. Until recently, Zhou co-workers7 achieved progress chiral using iridium bulky phosphine catalyst. nucleophilic addition organometallic reagents carbonyl provides another straightforward route; nevertheless, focused on nucleophiles. Despite achievements associated challenges, alternative utilize enantiomerically alcohol its derivative pursued. Scheme 1 | (a–d) State art Ni–H-initiated hydroalkylation. dtbbpy, 4,4′-di-tert-butyl-2,2′-bipyridine; Boc, tert-butyloxycarbonyl; ee = enantiomeric excess. Transition-metal-catalyzed carbon–carbon developed few decades become one most processes chemistry.8–10 Different from coupling reactions easily accessible stable arylation (e.g., arylboronic, etc.), there issues be addressed reactions, including accessibility control enantioselectivity.11–14 Benefiting starting olefins halides, alkene hydrogenation-coupling strategy emerged past 5 years as fascinating traditional electrophile-nucleophile cross-couplings, which could prevent necessity pre-preparing hyperactive improve group compatibility 1c).15–26 In 2016, our group27,28 established formation, namely, nonasymmetric version nickel-catalyzed electronically unbiased alkenes unactivated alkylmetallic equivalents. Concerning more valuable products, early examples functionalized halides general alkenes. G. C. Fu's group29,30, Zhu's 31, group32 independently enantioconvergent secondary even challenging tertiary29 electrophiles. Recently, several other groups became interested since both pathways provide analogous products.33,34 To certain extent, many α-heteroatom (N, O, S, etc.) prepare, readily than halide counterparts.35,36 Most Hu's group, Shu's carbon stereocenter controlled achiral enamides37–39 alkenyl boronates,40 namely enamides boronates produce amines boronates. context, envisioned new might realize direct derived 1d). uses generate via operations. is universal introducing α-position esters, it exhibits tolerance bearing varying groups; thus, complementing existing methods. still difficulties realizing design.41 Compared by et al.,8,11 center located ester, different well-known enantioselectivity radical corresponding electrophile pattern. Even successful not applied directly esters. electron density double boronate favored nickel into boron atom. comparison, had much positive electronegativity [see Supporting Information Section 10, Figures S5–S10 theory (DFT) calculations], implying unfavorable substrate. cases enecarbamates, coordination facilitates five-membered nickelacycle, leading α-selective insertion. oxygen atom weaker Lewis alkalinity enecarbamate, directing group.42 All vast differences chemical properties negative factors hydrometallation would adverse effect efficiency Experimental hydrocarbonation ethers air, NiCl2(PPh3)2 (0.020 mmol, 13.0 mg), dtbbpy (0.030 8.0 mg) (dtbbpy 4,4′-di-tert-butyl-2,2′-bipyridine), Na2CO3 (0.6 64.0 2a (0.4 125 added Schlenk tube equipped stir bar. evacuated filled argon (three cycles). solids, mL N,N-dimethylformamide (DMF)/H2O (v:v 1000:1, 0.2 M) atmosphere. Then, diethoxymethylsilane (DEMS) 96 μL) 1a (0.2 35 sequentially mixture stirred 40 °C 12 h purified column chromatography (silica gel; petroleum ether/ethyl acetate) afford desired product 3aa. More experimental details characterization available Information. Asymmetric (S,S- L1) 10.0 K3PO4(H2O) 92.0 62.5 2 N,N-dimethylacetamide (DMAc)/1,2-dichloroethane (DCE) 1:4, 0.1 atmosphere room temperature 10 min. (MeO)3SiH 76 1n 94.0 36 3na. Computational calculations performed Gaussian 16, Rev. C01. DFT B3LYP, Grimme empirical dispersion correction (GD3BJ), optimize all intermediates transition states' geometry. def2SVP basis set employed elements. solvent effects taken account solvation model based solute (SMD) 1,2-dichloroethane (CH2ClCH2Cl). Results Discussion Reaction We began study 3aa iodide (Table 1). determined efficiently nickel/bipyridine/triphenylphosphine catalyst DEMS DMF/H2O mixed (entry 1), impact each parameter summarized. Bidentate N-ligands gave adequate productivity, except sterically hindered ligand ortho-methyl groups. tridentate tested trace amounts products. Triphenylphosphine, system, due weak ability 2); stabilize Ni de-coordinate site.43 31P NMR studies, observed triphenylphosphine dissociate react water form oxide (see 8.4 details). Besides, showed excess NiBr2(diglyme) (diglyme 2-methoxyethyl ether) significantly yield 34% 71% 3). Nitrogen dual previous works Weix al.,44 Wang al.,45,46 group,28 respectively. Other salts used, led degrees reduced yields 2), but did take place without catalysts transition-metal Pd, Fe, Co, Cu) (entries 4 5). Similar studies,27,28,32 confirmed cross-combination bases silanes regulated activity 6–10). general, oxygen-bearing silane combined moderate base results. highly dependent solvents 11–13); obtained high-polarity [e.g., 1-methyl-2-pyrrolidinone (NMP), DMAc, CH3CN], while low lower-polarity DCE, tetrahydrofuran (THF), iPr2O, 1,4-dioxane]. Finally, microscale amount played role promoting 14), lower shut down 15–17). Table Optimization Conditions NiH-Catalyzed Hydrocarbonationa Entry Deviation Standard Yield (%) None 94 ( 90b) NiBr2(diglyme), NiI2(xH2O), Ni(OTf)2, NiCl2(dppp) instead 34–47 3 + 10% PPh3 71 Without N.R. PdCl2(PPh3)2, FeI2, CoBr2(DME), CuI 6 Ph2SiH2, DMMS, (MeO)3SiH, PMHS 61–85 7 MeEt2SiH 8 K3PO4(H2O), KHCO3, NaHCO3 73–77 9 NaF CsF 19–33 Mg(OAc)2(4H2O) <5 11 NMP, CH3CN DMF 61–86 THF, iPr2O 6–9 13 1,4-dioxane 14 moisture content 100:1, 500:1, 2000:1 1000:1 88–92 15 0 16 20 62 17 60 78 Note: Tf, triflyl; Ac, acetyl; dppp, 1,3-bis(diphenylphosphino)propane; DME, 1,2-dimethoxyethane; diglyme ether; 1-methyl-2-pyrrolidinone; N,N-dimethylacetamide; DMF, N,N-dimethylformamide; 1,2-dichloroethane; tetrahydrofuran; methyldimethoxysilane; DEMS, diethoxymethylsilane; PMHS, polymethylhydrosiloxane; N.R., no reaction. aConditions: (0.1 1.0 equiv), 2.0 (0.01 mol %), (0.015 (0.3 3.0 (0.5 mL, M), h. Bis(4-methoxyphenyl)methanone internal standard. Gas (GC) yield. bIsolated parentheses. Scope Having optimal conditions, investigated process. As shown 2, wide range partners examined, iodides bromides (with NaI additive) furnished gratifying results cases. A variety well accommodated, relatively robust ether 3aa, 3ad, 3ae), 3af 3ag), trifluoromethyl cyano 3ah 3ai) base-sensitive 3aj 3ak), aldehyde 3al), amide-possessing N–H 3am) compatible during transformation. Notably, chloride 3an), 3ao), bromide 3ap) survived, indicating chemoselectivity These surviving electrophilic sites provided possibility further manipulations. Heterocyclic such morpholine 3aq), thiophene 3ar), furan 3as), indole 3at), coumarin 3au) moieties posed problems. design medicine candidates, methylation commonly biological activities physical Thus, delighted iodomethane perdeuterated indeed substrates afforded 3av 3aw). extended 5aa 5ab) partner. limitation failure couple dehalogenation required optimization conditions. Also, fairly broad, single α-alkylation regioselectivity Both protecting example, less acetyl 3ba– 3ea), benzoyl 3fa), removed tert-butyloxycarbonyl 3ga) present. acyclic 3ha) cyclic 3ia) converted; exhibited higher reactivity. Various 3ja), phthalimide 3ka), 3la) exceptionally compatible. sensitive 3al 3az) offers appealing advantages over compounds. Further, silyl however, observe appreciable product; instead, large proportion material, ether, recovered. found applications late-stage modification complex bioactive molecules, exhibiting strong potential functionalization glucose 3ax), indomethacin 3ay), lithocholic acid 3az). Racemic Reactiona aStandard reaction: (0.02 (0.03 (1.0 v/v 1000:1), °C, h, isolated bNaI equiv) additive. cDiastereocenters marked spherical symbol. dr, diastereomeric ratio. Next, synthesize realized nickel/bisoxazoline L1)/triphenylphosphine trimethoxysilane DMAc/DCE Although vital unclear reaction, decisive component Two equivalents appropriate obtain scoping variant summarized 3. tert-butyloxycarbonyl-protected enols smoothly coupled deliver (30–52% yield) uniformly enantioinduction [88–97% (ee)]. Z/E configuration affect progressed tolerated those 3na, 3nd, 3ge, 3ra), 3nA), 3nC), 3nh), protected arylamine 3nm). Moreover, tosylate 3oD) 3sa) survived being converted reactions. hydroarylation. Fortunately, benzyl easy well-developed strategies.47,48 feasibility constructing carbinol supplement long-standing methods, S3 S4 Tables S1–S5 assignment absolute 3na). Hydroalkylation (S,S)- L1 (2.0 1:4), Ts, tosyl. mechanism conventional experiments 2). clock experiment 2a) 5-iodopent-1-ene 2E), assumed 3aE′ 3aE″ observed, linear 3aE) produced migration bond. 2F) containing cyclopropyl ring. ring-opened 3aF) 63% yield, terminal migrated. From above results, concluded pathway involved activation considerably fast step. carried out deuterium-labeling stereochemistry 2b). Deuterated hydrosilane (Ph2SiD2) standard deuterium incorporation β-position acyloxy H/D exchange noted α- γ- positions indicated insertion across regioselective irreversible. matched ratio 1n) diastereoselectivity deuterated (d1- 3nv d1- 3nv′) isomerization occur. addition, equilibrium pair low-valent oxoalkyl homolysis Ni–C excluded.49,50 Collectively, stereochemical revealed α-oxoalkyl diastereoselectivity. low-temperature (10 K) X-band paramagnetic resonance (EPR) analyze after times.51–53 EPR spectrum (top four lines) simulation spectra (bottom 2c Figure S2 At initial state (1 min), typical low-spin signal g values 2.27 2.02, Ni(II) Ni(I) state. proceeded, vanished Ni(III) appeared peaks 2.20 1.99. amplitude reached maximum about gradually decreased. end (420 returned +2 valence state, "EPR-silent" X-band. spin-trapping characterized times 2d) S1 presence spin trapping agent 5,5-dimethyl-1-pyrroline N-oxide (DMPO) (1) 30 min (3) measured (2) (4) shown. satisfactorily simulated three components, (5) DMPO-H, aN 14.77 G, aH 19.90 G (2 β-H atoms); (6) DMPO-R1, 14.57 17.63 G; (7) DMPO-R2, 14.53 20.76 collected components following ratio: DMPO-R1:DMPO-R2:DMPO-H 0.2:0.7:0.1, 0.39:0.47:0.14. Note added, likely caused competitive destroyed elimination step.54–57 convincing data, difficult clearly understand mechanism. particular, clarify fundamentals change states With help literature,16,29,32,51,58,59 proposed presumptive radical-chain (left, 2e), follows: First, ligand-bound nickel(I) A) active nickel(II) salt B). Second, resultant B) reacted formed hydride C). Then C) incorporated organonickel(II) D). Third, recombination E). E) underwent regenerated A), closing cycle. enantioselectivity-controlling step proved enantioselectivity, studies.29,31,60,61 2e (right). mechanistic groups.33,34 First all, A′) reduction resulting A′ B′). Nickel(I) B′ inserted C′). Subsequent oxidative D′), finish cross-coupling. (a–e) Preliminary Conclusion describe method user-friendly alkylation aryla

Language: Английский

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Enantioselective Synthesis of Pyridines with All‐Carbon Quaternary Carbon Centers via Cobalt‐Catalyzed Desymmetric [2+2+2] Cycloaddition

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(37), P. 20204 - 20209

Published: July 2, 2021

Abstract A Co‐catalyzed enantioselective desymmetric [2+2+2] cycloaddition for synthesis of pyridines with all‐carbon quaternary carbon centers has been developed. The regio‐ and enantioselectivities are controlled by the inherent nature terminal alkynes substituents on bisoxazolinephosphine ligands. Pyridines 5‐substitutents could be obtained >20:1 regioselectivity up to 94 % ee when alkyl, alkenyl or silyl DTBM/Ph‐based NPN* ligand L6 were used. Terminal aryl Ph/Bn‐based L4 leads formation 6‐substitutents in 99 .

Language: Английский

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Iron-Catalyzed Highly Enantioselective Hydrogenation of Alkenes

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(32), P. 12433 - 12438

Published: Aug. 3, 2021

Here, we reported for the first time an iron-catalyzed highly enantioselective hydrogenation of minimally functionalized 1,1-disubstituted alkenes to access chiral alkanes with full conversion and excellent ee. A novel 8-oxazoline iminoquinoline ligand its iron complex have been designed synthesized. This protocol is operationally simple by using 1 atm hydrogen gas shows good functional group tolerance. primary mechanism has proposed deuterium-labeling experiments.

Language: Английский

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